For US Healthcare Professionals

For US HCPs

SIGN up for updates
Know Hep B Testing logo
SIGN up for updates
    SIGN up for updates

    KEY BIOMARKER: Quantitative and qualitative HBsAg testing

    HBsAg testing in the management of chronic hepatitis B (CHB)

    • HBsAg is a viral surface protein and an important marker of active chronic HBV infection1
    • It is a measure of the total transcriptional activity of both covalently closed circular DNA (cccDNA) and integrated HBV DNA in liver cells2
    • HBsAg is believed to promote immune evasion and disease chronicity2

    HBsAg tests for CHB:

     

    Qualitative HBsAg
    Detects only presence or absence of HBsAg in serum via standard immunoassays (eg, ELISA, CLIA)2,3

    Clinical utility3-5:

    • Initial diagnosis of HBV and screening for at-risk individuals
    • Cannot inform disease activity, treatment response, or prognosis, except in rare cases of HBsAg loss
    Quantitative HBsAg
    Measures serum concentration of HBsAg in IU/mL via automated immunoassay6,7

    Clinical utility3:

    • Quantitative HBsAg (qHBsAg) testing may help deliver more comprehensive evaluation—informing prognosis, treatment decisions, and tracking progress toward functional cure*

    Clinical utility of quantitative HBsAg (qHBsAg)

    qHBsAg may help inform clinical decisions

    Inform treatment eligibility

    • Support shared decision-making and guiding clinical decisions in HBeAg-negative grey-zone patients5†
    • Identify true inactive HBV carriers and those at risk of disease progression5

    Monitor treatment response and cessation

    • Help assess progress toward functional cure3,7,8*
    • Support decisions on NA cessation3,7,8

    Provide prognostic value

    • Evaluate probability of spontaneous HBsAg loss5
    • Predict risk of liver fibrosis and HCC5

    Quantitative HBsAg and its interpretation:

    qHBsAg Interpretation Cirrhosis risk3 HCC risk3
    Below reference5,9
    (<100 IU/mL)    		 Suggests inactive CHB
    • Risk of viral relapse reduced, varying by ethnicity
    • Increases the specificity of identifying patients with inactive CHB, but reduces sensitivity to 35%
    		 HR 1
    (reference)    		 HR 1
    (reference)
    Low5
    (100–<1,000 IU/mL)    		 Suggests inactive CHB
    • May predict spontaneous HBsAg clearance in HBeAg-negative patients with a low viral load
    • May require less frequent monitoring
    		 HR 1.96 HR 3.2
    Elevated3
    (≥1,000 IU/mL)    		 Elevated risk of cirrhosis and HCC HR 3.5 HR 5.4

    HBsAg loss may be associated with improved clinical outcomes7,10,11

    Two studies examined the relationship between HBsAg loss and its association
with long-term outcomes10,11

    In a retrospective cohort study that examined 15,760 patients living with CHB, HBsAg loss was associated with10:

    89%

    REDUCED RISK
    
of HCC

    aHR=0.11 (95% CI: 0.01–0.76)

    62%

    REDUCED RISK
    
of all-cause mortality

    aHR=0.38 (95% CI: 0.20–0.74) 

    In a separate retrospective cohort study of 20,263 patients, HBsAg loss was associated with11:

    76%

    REDUCTION

    in HCC risk

    after 8 years of follow-up, compared with complete viral suppression alone.

    aHR=0.24 (95% CI: 0.06–0.97; P=0.045)

    HBsAg loss can also be used to determine when a
patient can discontinue NA therapy.7,8

    HBsAg loss and treatment discontinuation are key components
of functional cure7,8

     

    As treatment goals evolve, functional cure is increasingly becoming
recognized as a treatment goal for CHB.7,8

    Functional cure is defined as sustained loss of HBsAg (<0.05 IU/mL) and undetectable HBV DNA (<10 IU/mL), maintained for 6 months post–treatment cessation.3,7

    *Functional cure is defined as sustained loss of HBsAg (<0.05 IU/mL) and undetectable HBV DNA (<10 IU/mL), maintained for 6 months post–treatment cessation.3,7

    †"Grey zone" is defined as HBeAg-positive or -negative with HBV DNA level and/or ALT level outside those with immune-tolerant, immune-active, or inactive CHB.8

    aHR=adjusted hazard ratio; ALT=alanine aminotransferase; CI=confidence interval; CLIA=chemoluminescence immunoassay; DNA=deoxyribonucleic acid; ELISA=enzyme-linked immunosorbent assay; HBeAg=hepatitis B e-antigen; HBsAg=hepatitis B surface antigen; HBV=hepatitis B virus; HCC=hepatocellular carcinoma; HR=hazard ratio; NA=nucleos(t)ide analog.

    Learn about HBeAg as a biomarker

    EXPLORE HBeAg

    References

    1. Clinical testing and diagnosis for hepatitis B. Centers for Disease Control and Prevention. January 31, 2025. Accessed April 5, 2026. https://www.cdc.gov/hepatitis-b/hcp/diagnosis-testing/index.html 

    2. Lin CL, Kao JH. Clin Mol Hepatol. 2016;22(4):423-431.

    3. Ghany MG, Buti M, Lampertico P, Lee HM; 2022 AASLD-EASL HBV-HDV Treatment Endpoints Conference Faculty. J Hepatol. 2023;79(5):1254-1269.

    4. Screening and testing for hepatitis B virus infection: CDC recommendations – United States, 2023. Centers for Disease Control and Prevention. March 10, 2023. Accessed April 5, 2026. https://www.cdc.gov/mmwr/volumes/72/rr/rr7201a1.htm 

    5. Terrault NA, et al. Hepatology. 2018;67(4):1560-1599. 

    6. Additional hepatitis B blood tests. Hepatitis B Foundation. Accessed April 5, 2026. https://www.hepb.org/prevention-and-diagnosis/diagnosis/hepatitis-b-blood-tests/ 

    7. European Association for the Study of the Liver. J Hepatol. 2025;83(2):502-583. 

    8. Ghany MC, et al. Hepatology. 2026;83(4):974-997. 

    9. Yang HC. Clin Liver Dis (Hoboken). 2024;23(1):e0195. 

    10. Drysdale M, et al. Association of hepatitis B surface antigen loss with long-term clinical outcomes among patients with chronic hepatitis B infection: a US-based retrospective cohort study using Optum electronic health records database. Presented at: Global Hepatitis Summit; March 18-21, 2025; Los Angeles, CA. 

    11.  Yip TCF, et al. J Hepatol. 2019;70(3):361-370.